Blood lactate assessment is standard for diagnosing suspected sepsis, though its use for guiding therapy is supported by weak, low-quality evidence, as elevated levels do not always indicate tissue hypoperfusion. Trials of early goal-directed therapy focusing on central venous oxygen saturation have shown no benefit over standard care. Alternatives, ranging from physical examination markers like capillary refill time and mottling to objective parameters or biomarkers such as the veno-arterial carbon dioxide gap, near-infrared spectroscopy, and active renin, are emerging. Given the variability in effective perfusion markers, this section will summarize the evidence to better understand the role of lactate levels and identify which other markers are suitable for guiding initial resuscitation in septic shock.